On October 7, 2024 MediLink Therapeutics (Suzhou) Co., Ltd. ("MediLink"), a clinical-stage biotech company, reported a global clinical trial collaboration and supply agreement with Amgen Inc. Amgen will lead a global clinical study to evaluate the therapeutic potential of the combination of MediLink’s B7-H3-targeting antibody-drug conjugate (ADC) YL201 and Amgen’s DLL3- and CD3-targeting bispecific T-cell engager (BiTE) IMDELLTRA in extensive-stage small cell lung cancer (ES-SCLC) under the clinical trial collaboration and supply agreement (Press release, Amgen, OCT 7, 2024, View Source [SID1234647073]). MediLink will provide the investigational drug YL201 for the combination study.

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This open-label, global, multi-center Phase Ib clinical study is designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of this combination regimen in ES-SCLC patients.

Both YL201 and IMDELLTRA have shown potential in ES-SCLC. In May of this year, IMDELLTRA received accelerated approval from the FDA and is currently marketed in the US for the treatment of adult patients with ES-SCLC with disease progression on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). The efficacy of YL201 monotherapy is encouraging in ES-SCLC. MediLink has announced the data of a Phase I/II clinical trial of YL201 in patients with advanced solid tumors including SCLC as a selected oral presentation at the ESMO (Free ESMO Whitepaper) Congress 2024. This clinical trial collaboration aims to explore the potential of the two innovative drugs in the treatment of ES-SCLC and offer a novel and synergetic mechanism of action for clinical benefit.

About ES-SCLC

SCLC is an aggressive high-grade neuroendocrine carcinoma with extremely poor outcomes [1]. SCLC comprises roughly 15% (~0.36 million new cases) of the 2.4 million new lung cancer cases worldwide each year [2].

Approximately two-thirds of patients with SCLC present with extensive-stage (ES) disease at diagnosis, featuring tumors with distant metastasis or exceeding an area that can be treated within a single radiation field [3-5]. Patients with ES-SCLC, compared with patients with limited-stage (LS-SCLC), manifested with worse prognosis as the median expected overall survival is ~12 months following initial therapy and a 5-year overall survival rate of 3% [6-8].

About YL201

YL201 is an innovative ADC that specifically targets B7-H3. B7-H3 is overexpressed on different malignant cells and cancer-initiating cells of various tumor types, but has a restricted expression in normal tissue [9], indicating its potential as an ADC drug target. YL201 has been developed by utilizing MediLink’s Tumor Microenvironment Activable LINker-payload (TMALIN) conjugated with a highly specific B7-H3 antibody. Currently, YL201 is being investigated in four Phase I or II studies, including one global Phase I clinical study.

About IMDELLTRA

IMDELLTRA is a first-in-class, targeted immunotherapy engineered by Amgen researchers that binds to both DLL3 on tumor cells and CD3 on T cells, activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell [10-11]. DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an exciting target [12-13].

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRATM. Initiate treatment with IMDELLTRATM using the step-up dosing schedule to reduce the incidence and severity of CRS. Withhold IMDELLTRATM until CRS resolves or permanently discontinue based on severity.
Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRATM. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment and treat promptly. Withhold IMDELLTRATM until ICANS resolves or permanently discontinue based on severity.
WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome (CRS): IMDELLTRATM can cause CRS including serious or life-threatening reactions. In the pooled safety population, CRS occurred in 55% of patients who received IMDELLTRATM, including 34% Grade 1, 19% Grade 2, 1.1% Grade 3 and 0.5% Grade 4. Recurrent CRS occurred in 24% of patients, including 18% Grade 1 and 6% Grade 2.
Most events (43%) of CRS occurred after the first dose, with 29% of patients experiencing any grade CRS after the second dose and 9% of patients experiencing CRS following the third dose or later. Following the Day 1, Day 8, and Day 15 infusions, 16%, 4.3% and 2.1% of patients experienced ≥ Grade 2 CRS, respectively. The median time to onset of all grade CRS from most recent dose of IMDELLTRATM was 13.5 hours (range 1 to 268 hours). The median time to onset of ≥ Grade 2 CRS from most recent dose of IMDELLTRATM was 14.6 hours (range: 2 to 566 hours).

Clinical signs and symptoms of CRS included pyrexia, hypotension, fatigue, tachycardia, headache, hypoxia, nausea, and vomiting. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).

Administer IMDELLTRATM following the recommended step-up dosing and administer concomitant medications before and after Cycle 1 IMDELLTRATM infusions as described in Table 3 of the Prescribing Information (PI) to reduce the risk of CRS. Administer IMDELLTRATM in an appropriate health care facility equipped to monitor and manage CRS. Ensure patients are well hydrated prior to administration of IMDELLTRATM.

Closely monitor patients for signs and symptoms of CRS during treatment with IMDELLTRATM. At the first sign of CRS, immediately discontinue IMDELLTRATM infusion, evaluate the patient for hospitalization and institute supportive care based on severity. Withhold or permanently discontinue IMDELLTRATM based on severity. Counsel patients to seek medical attention should signs or symptoms of CRS occur.

Neurologic Toxicity, Including ICANS: IMDELLTRATM can cause serious or life-threatening neurologic toxicity, including ICANS. In the pooled safety population, neurologic toxicity, including ICANS, occurred in 47% of patients who received IMDELLTRATM, including 10% Grade 3. The most frequent neurologic toxicities were headache (14%), peripheral neuropathy (7%), dizziness (7%), insomnia (6%), muscular weakness (3.7%), delirium (2.1%), syncope (1.6%), and neurotoxicity (1.1%).
ICANS occurred in 9% of IMDELLTRATM-treated patients. Recurrent ICANS occurred in 1.6% of patients. Most patients experienced ICANS following Cycle 2 Day 1 (24%). Following Day 1, Day 8, and Day 15 infusions, 0.5%, 0.5% and 3.7% of patients experienced ≥ Grade 2 ICANS, respectively. The median time to onset of ICANS from the first dose of IMDELLTRATM was 29.5 days (range: 1 to 154 days). ICANS can occur several weeks following administration of IMDELLTRATM. The median time to resolution of ICANS was 33 days (range 1 to 93 days).

The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia.

Patients receiving IMDELLTRATM are at risk of neurologic adverse reactions and ICANS resulting in depressed level of consciousness. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, in the event of any neurologic symptoms until they resolve.

Closely monitor patients for signs and symptoms of neurologic toxicity and ICANS during treatment. At the first sign of ICANS, immediately evaluate the patient and provide supportive therapy based on severity. Withhold IMDELLTRATM or permanently discontinue based on severity.

Cytopenias: IMDELLTRATM can cause cytopenias including neutropenia, thrombocytopenia, and anemia. In the pooled safety population, decreased neutrophils occurred in 12% including 6% Grade 3 or 4 of IMDELLTRATM-treated patients. The median time to onset for Grade 3 or 4 neutropenia was 29.5 days (range: 2 to 213). Decreased platelets occurred in 33% including 3.2% Grade 3 or 4. The median time to onset for Grade 3 or 4 decreased platelets was 50 days (range: 3 to 420). Decreased hemoglobin occurred in 58% including 5% Grade 3 or 4. Febrile neutropenia occurred in 0.5% of patients treated with IMDELLTRATM.
Monitor patients for signs and symptoms of cytopenias. Perform complete blood counts prior to treatment with IMDELLTRATM, before each dose, and as clinically indicated. Based on the severity of cytopenias, temporarily withhold, or permanently discontinue IMDELLTRATM.

Infections: IMDELLTRATM can cause serious infections, including life-threatening and fatal infections. In the pooled safety population, infections, including opportunistic infections, occurred in 41% of patients who received IMDELLTRATM. Grade 3 or 4 infections occurred in 13% of patients. The most frequent infections were COVID-19 (9%, majority during the COVID-19 pandemic), urinary tract infection (10%), pneumonia (9%), respiratory tract infection (3.2%), and candida infection (3.2%).
Monitor patients for signs and symptoms of infection prior to and during treatment with IMDELLTRATM and treat as clinically indicated. Withhold or permanently discontinue IMDELLTRATM based on severity.

Hepatotoxicity: IMDELLTRATM can cause hepatotoxicity. In the pooled safety population, elevated ALT occurred in 42%, with Grade 3 or 4 ALT elevation occurring in 2.1%. Elevated AST occurred in 44% of patients, with Grade 3 or 4 AST elevation occurring in 3.2%. Elevated bilirubin occurred in 15% of patients; Grade 3 or 4 total bilirubin elevations occurred in 1.6% of patients. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin prior to treatment with IMDELLTRATM, before each dose, and as clinically indicated. Withhold IMDELLTRATM or permanently discontinue based on severity.
Hypersensitivity: IMDELLTRATM can cause severe hypersensitivity reactions. Clinical signs and symptoms of hypersensitivity may include, but are not limited to, rash and bronchospasm. Monitor patients for signs and symptoms of hypersensitivity during treatment with IMDELLTRATM and manage as clinically indicated. Withhold or consider permanent discontinuation of IMDELLTRATM based on severity.
Embryo-Fetal Toxicity: Based on its mechanism of action, IMDELLTRATM may cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMDELLTRATM and for 2 months after the last dose.
ADVERSE REACTIONS

The most common (> 20%) adverse reactions were CRS (55%), fatigue (51%), pyrexia (36%), dysgeusia (36%), decreased appetite (34%), musculoskeletal pain (30%), constipation (30%), anemia (27%) and nausea (22%). The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (57%), decreased sodium (16%), increased uric acid (10%), decreased total neutrophils (6%), decreased hemoglobin (5%), increased activated partial thromboplastin time (5%), decreased potassium (5%), increased aspartate aminotransferase (3.2%), decreased white blood cells (3.8%), decreased platelets (3.2%), and increased alanine aminotransferase (2.1%).
Serious adverse reactions occurred in 58% of patients. Serious adverse reactions in > 3% of patients included CRS (24%), pneumonia (6%), pyrexia (3.7%), and hyponatremia (3.6%). Fatal adverse reactions occurred in 2.7% of patients including pneumonia (0.5%), aspiration (0.5%), pulmonary embolism (0.5%), respiratory acidosis (0.5%), and respiratory failure (0.5%).
DOSAGE AND ADMINISTRATION: Important Dosing Information

Administer IMDELLTRATM as an intravenous infusion over one hour.

Administer IMDELLTRATM according to the step-up dosing schedule in the IMDELLTRATM PI (Table 1) to reduce the incidence and severity of CRS.
For Cycle 1, administer recommended concomitant medications before and after Cycle 1 IMDELLTRATM infusions to reduce the risk of CRS reactions as described in the PI (Table 3).
IMDELLTRATM should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity including ICANS.
Due to the risk of CRS and neurologic toxicity, including ICANS, monitor patients from the start of the IMDELLTRATM infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting.
Recommend that patients remain within 1 hour of an appropriate healthcare setting for a total of 48 hours from start of the infusion with IMDELLTRATM following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver.
Prior to administration of IMDELLTRATM evaluate complete blood count, liver enzymes, and bilirubin before each dose, and as clinically indicated.
Ensure patients are well hydrated prior to administration of IMDELLTRATM.
Please see IMDELLTRA full Prescribing Information, including BOXED WARNINGS

On October 7, 2024 Compugen Ltd. (Nasdaq: CGEN) (TASE: CGEN) a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, reported that new clinical data supporting the anti-tumor activity and safety of the triple combination COM701, COM902 and pembrolizumb in heavily pre-treated patients with platinum resistant ovarian cancer will be presented at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), taking place between November 8-10, 2024, in Houston, Texas (Press release, Compugen, OCT 7, 2024, View Source [SID1234647072]).

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Poster presentation details:

Abstract Title: Triple blockade of DNAM-1axis with COM701 (anti-PVRIG) + COM902 (anti-TIGIT) + pembrolizumab shows preliminary antitumor activity in patients with platinum resistant ovarian cancer, interim results of Phase I trial
Abstract number: 985
Presenter: Dr. Oladapo Yeku, Medical Oncologist, Massachusetts General Hospital
Date: Friday, November 8, 2024

On October 7, 2024 GBI Biomanufacturing, a leading Contract Development and Manufacturing Organization (CDMO), and Allterum Therapeutics, a Fannin-Founded Company, reported a manufacturing partnership to advance Allterum’s lead candidate 4A10 into clinic (Press release, Allterum, OCT 7, 2024, View Source [SID1234647071]). 4A10 is a monoclonal antibody (mAb) targeting CD127, a receptor expressed by a broad variety of cancers.

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With this collaboration, GBI will leverage their extensive expertise in manufacturing complex biologics to ensure the high-quality production of 4A10 for Phase 1/2a clinical trials. Allterum’s initial trial will focus on patients who have acute lymphoblastic leukemia (ALL), with subsequent expansion to trials in patients with other CD127-expressing hematological malignancies, including lymphomas and acute myeloid leukemia.

"We are honored to be chosen by Allterum as their trusted partner on this important project," said Karl Pinto, Chairman and CEO of GBI. "Our team is dedicated to providing the highest quality development and manufacturing services for drug substance and drug product, ensuring the success of this promising treatment. This collaboration is a testament of our commitment to advancing the field of oncology and making a meaningful difference in the lives of patients."

Atul Varadhachary, Allterum’s CEO and Managing Partner at Fannin added, "4A10 has demonstrated robust preclinical activity across multiple cancers and we are excited about advancing it into clinic. We selected GBI as our manufacturing partner based on their years of experience with complex biologics, and we look forward to working together to ensure our program’s success."

Allterum’s 4A10 development program is supported by grant funding from the Cancer Prevention and Research Institute of Texas (CPRIT), the National Cancer Institute (NCI) and additionally has been supported through the NCI Experimental Therapeutics Program (NExT). The antibody, invented at the NCI by senior investigator Scott Durum, PhD and his collaborators, is licensed exclusively to Allterum. Allterum has received Orphan Drug and Rare Pediatric Disease designations for ALL from the FDA, which will provide facilitated access to the FDA and potentially qualify 4A10 for a Pediatric Priority Review Voucher.

Successful completion of Allterum’s Phase 1/2a clinical trials will mark a significant milestone in developing this promising anti-cancer drug, addressing major unmet medical needs.

On October 7, 2024 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncologic, autoimmune, cardiovascular and metabolic, ophthalmologic and other major diseases, and Jiangsu Aosaikang Pharmaceutical Co. Ltd. (ASK Pharm, 002755.SZ), reported that the two parties have entered into a strategic collaboration regarding limertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for the treatment of lung cancer (Press release, Innovent Biologics, OCT 7, 2024, View Source [SID1234647070]).

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Under the agreement, Innovent will obtain the exclusive commercialization rights for limertinib in mainland China, and will be entitled to receive a commercialization service fee based on the product’s net sales in the region. Ask-Pharm as the MAH holder, will be responsible for the production and commercial supply of limertinib and will be eligible for upfront, regulatory and sales milestone payments.

Limertinib is an orally administrated, third-generation novel EGFR TKI with proprietary rights. Two New Drug Applications (NDAs) for limertinib have been accepted and are under review by China’s National Drug Administration (NMPA): (1) for the treatment of adult patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC, confirmed by a validated diagnostic test, whose disease has progressed after EGFR TKI therapy; and (2) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.

In a multi-center, randomized, double-blind, controlled Phase 3 clinical trial, limertinib’s efficacy and safety were compared with gefitinib in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR mutations. The Phase 3 clinical trial met its primary endpoint, and detailed data and analysis will be presented at future academic conferences or published in academic journals. Previously, results of limertinib from a Phase 2b clinical study were presented in a poster session at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

Dr. Michael Yu, Founder, Chairman and CEO of Innovent, stated: "We are delighted to enter this strategic collaboration with ASK Pharm, one of the most innovative biopharmaceutical companies in China, which will further strengthen Innovent’s leadership in oncology. Together with our partners, Innovent has successfully developed a series of high-quality innovative medicines for lung cancer treatments, including TYVYT (sintilimab Injection), BYVASDA (bevacizumab Injection), Retsevmo (selpercatinib), Dupert (fulzerasib) and Taletrectinib (ROS1 Inhibitor, NDA under review). The addition of limertinib will offer a valuable new treatment option for Chinese patients with EGFR-mutated lung cancer. Innovent remains committed to investing in innovation and collaborative partnerships, aiming to enhancing the accessibility and affordability of innovative therapies in China to benefit even more patients."

Mr. Jingfei Ma, Director and General Manager of ASK Pharm, stated: "We are pleased to form a strategic partnership with Innovent Biologics. Oncology is one of the four core areas of focus for ASK Pharm, and our oncology product line spans chemotherapy drugs, small molecule targeted drugs, and biologics. Limertinib, ASK Pharm’s first innovative drug, targets the cancer type with the highest incidence and mortality rates in China. Focused on addressing the most common mutations in lung cancer, Ask-Pharm is committed to providing effective drugs for the vast number of patients with EGFR-mutated lung cancer. Innovent has a rich product pipeline in the field of lung cancer, which can form advantageous synergies with limertinib. In addition, with Innovent’s professional and efficient marketing team and proven commercialization capabilities, we are confident that this cooperation will help limertinib to fully realize its clinical value, so that more patients can benefit from it."

About EGFR mutation-positive non-small-cell lung cancer (NSCLC)

Lung cancer is the leading cause of cancer-related death and the second more common cancer worldwide. In China, it has both the highest incidence and mortality rates among malignant tumors. Non-small cell lung cancer (NSCLC) accounts for approximately 80% to 85% of all lung cancers, and approximately 70% of NSCLC patients are diagnosed with locally advanced or metastatic disease that is not eligible to surgical resection. EGFR is the most frequent driver mutation in NSCLC, with 30% to 50% of Asian NSCLC patients having EGFR mutations. EGFR-TKIs are the recommended first-line standard of care for this group, with third-generation EGFR inhibitors offering the broadest applicability.

About Limertinib

Limertinib is an orally-administrated, third-generation EGFR TKI with proprietary rights, classified as a new molecular entity. Two New Drug Applications (NDAs) of limertinib are currently under review by China’s National Drug Administration (NMPA): (1) for the treatment of adult patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC, confirmed by an approved test, whose disease has progressed following EGFR TKI therapy; and (2) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.

In a multi-center, randomized, double-blind, controlled Phase 3 clinical trial, the efficacy and safety of limertinib were compared to gefitinib in the first-line treatment of patients with locally advanced or metastatic NSCLC harboring EGFR mutations. The Phase 3 clinical trial met its primary endpoint, and the results will be presented at future academic conferences or published in academic journals. Results from a Phase 2b clinical study were presented in a poster session at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

In October 2024, Innovent and ASK Pharm entered into a strategic collaboration and license agreement regarding limertinib in mainland China.

On October 7, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily for malignancies, reported that APG-2449, a FAK/ALK/ROS1 tyrosine kinase inhibitor (TKI), has been cleared by the Center for Drug Evaluation (CDE) of China’s National Medical Product Administration (NMPA) to enter two registrational Phase III studies that will separately evaluate APG-2449 in patients with non-small cell lung cancer (NSCLC) who are resistant to or intolerant of second-generation anaplastic lymphoma kinase (ALK) TKIs; and treatment-naïve patients with ALK-positive advanced or locally advanced NSCLC (Press release, Ascentage Pharma, OCT 7, 2024, View Source [SID1234647069]).

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These two pivotal studies will be multicenter, open-label, randomized, registrational Phase III studies: first one is to evaluate the efficacy and safety of APG-2449 versus platinum-based chemotherapies in patients with NSCLC who are resistant to or intolerant of second-generation ALK TKIs. The second registrational Phase III study is designed to evaluate the efficacy and safety of APG-2449 versus crizotinib as frontline therapies for treatment-naïve patients with ALK-positive advanced or locally advanced NSCLC. These two studies are the studies of an investigational drug not yet approved by the FDA in the US.

ALK-positive NSCLC is a type of lung cancer with a specific molecular profile characterized by the abnormal arrangement or the fusion of the ALK gene which occurs in approximately 3%-5% of all lung cancer cases. Most patients with ALK-positive NSCLC are relatively young, non-smoking or only have a light smoking history, and have a higher risk of brain metastasis.

Despite that multiple ALK-targeted therapies have already been approved, more than half of patients with NSCLC treated with second-generation ALK TKIs would develop acquired resistance, thus the Chinese Society of Clinical Oncology (CSCO) guidelines’ recommendation of platinum-based chemotherapies as a treatment option for patients who had failed on second-generation ALK-targeted therapies. It is widely acknowledged that chemotherapies are commonly associated with strong side effects and there is a growing general preference for chemotherapy-free regimens for the treatment of advanced tumors. Therefore, patients with resistance to second-generation ALK TKIs have an enormous unmet clinical need for new therapies that are effective and safe.

APG-2449, developed by Ascentage Pharma, is an orally-active small molecule FAK inhibitor and a third-generation ALK/ROS1 TKI, and the first FAK inhibitor cleared by the CDE to enter clinical study in China. In the first-in-human trial, APG-2449 demonstrated preliminary clinical benefit and favorable tolerability in patients with NSCLC who were either second-generation ALK TKI resistant or treatment-naïve. APG-2449 also showed potential inhibitory effect on brain metastases, with its ability to cross the blood-brain barrier confirmed through pharmacokinetics (PK) analysis on cerebrospinal fluid. Biomarker analysis found that the phosphorylated FAK (pFAK) expression in tumor tissues at baseline in patients with NSCLC who were second-generation ALK TKI-resistant, were positively correlated with the progress-free survival (PFS) after treatment with APG-2449, indicating that elevated phosphorylated FAK could be associated with drug resistance to second-generation ALK TKIs.

Prof. Li Zhang, the principal investigator of these two registrational Phase III studies from Sun Yat-sen University Cancer Center, commented, "APG-2449 is an effective multitargeted inhibitor that acts on FAK/ALK/ROS1. In previously released clinical data, APG-2449 consistently showed manageable safety and favorable antitumor activity in patients with NSCLC. We are particularly encouraged by the preliminary efficacy observed in patients with resistance to second-generation ALK TKIs, as it suggests that multitargeted inhibition on FAK and ALK may offer a new strategy for the management of patients with NSCLC resistant to second-generation ALK TKIs. We look forward to initiating the two registrational Phase III studies of APG-2449 in order to further validate the drug candidate and allow more patients to benefit from this novel therapeutic agent as soon as possible."

"There is considerable unmet clinical need in the field of NSCLC. APG-2449, a FAK/ALK/ROS1 TKI, has already showed its therapeutic potential in the released clinical data," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "The CDE’s approvals for the two registrational Phase III studies of APG-2449 are very encouraging as they mark a major milestone in the drug candidate’s clinical development. To fulfill our mission of addressing unmet clinical needs in China and around the world, we will expeditiously advance these clinical development programs for the benefit of more patients."